De Novo Summary (DEN170018) Page 1 of 1 DE NOVO CLASSIFICATION REQUEST FOR NSS-2 BRIDGE REGULATORY INFORMATION FDA identifies this generic type of device as: Percutaneous nerve stimulator for substance use disorders. A percutaneous nerve stimulator for substance use disorders is a device that stimulates nerves percutaneously to aid in the reduction of withdrawal symptoms associated with substance use disorders. NEW REGULATION NUMBER: 21 CFR 882.5896 CLASSIFICATION: Class II PRODUCT CODE: PZR BACKGROUND DEVICE NAME: NSS-2 BRIDGE SUBMISSION NUMBER: DEN170018 DATE OF DE NOVO: March 17, 2017 CONTACT: Innovative Health Solutions (IHS), Inc. 829 South Adams St. Versailles, IN 47042 INDICATIONS FOR USE The NSS-2 BRIDGE is a percutaneous nerve field stimulator (PNFS) system, that can be used as an aid to reduce the symptoms of opioid withdrawal, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination. LIMITATIONS For prescription use only. The device is contraindicated for use by patients with cardiac pacemakers, hemophilia, and psoriasis vulgaris. The device should only be applied to healthy, clean, intact skin. The device therapy is limited to 120 hours, after which the device is disposable.
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De Novo Summary (DEN170018) Page 1 of 1
DE NOVO CLASSIFICATION REQUEST FOR NSS-2 BRIDGE
REGULATORY INFORMATION FDA identifies this generic type of device as:
Percutaneous nerve stimulator for substance use disorders. A percutaneous nerve stimulator for substance use disorders is a device that stimulates nerves percutaneously to aid in the reduction of withdrawal symptoms associated with substance use disorders.
NEW REGULATION NUMBER: 21 CFR 882.5896 CLASSIFICATION: Class II PRODUCT CODE: PZR
BACKGROUND
DEVICE NAME: NSS-2 BRIDGE
SUBMISSION NUMBER: DEN170018 DATE OF DE NOVO: March 17, 2017 CONTACT: Innovative Health Solutions (IHS), Inc.
829 South Adams St. Versailles, IN 47042
INDICATIONS FOR USE The NSS-2 BRIDGE is a percutaneous nerve field stimulator (PNFS) system, that can be used as an aid to reduce the symptoms of opioid withdrawal, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination.
LIMITATIONS
For prescription use only. The device is contraindicated for use by patients with cardiac pacemakers, hemophilia, and psoriasis vulgaris. The device should only be applied to healthy, clean, intact skin. The device therapy is limited to 120 hours, after which the device is disposable.
De Novo Summary (DEN170018) Page 2 of 2
The appliance is splash-proof but not watertight. When showering, the device must not be allowed to come into direct contact with water. PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION NSS-2 BRIDGE is a device that electrically stimulates branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination through percutaneous electrodes to aid in the reduction of opioid withdrawal symptoms. The device consists of (1) a percutaneous nerve field stimulator (PNFS; Figure 1), (2) a multi-pin wire harness percutaneous electrode array (Figure 2), and (3) a pen light for use in the transillumination technique that aids in positioning of the percutaneous electrodes (Figure 3).
Figure 1: Percutaneous nerve field stimulator (PNFS)
The wire harness percutaneous electrode array consists of 4 leads. The 1-1-1-4 configuration consists of three single-needle leads, and one 4-needle array (Figure 2).
Figure 2: 1-1-1-4 Wire Harness configuration
De Novo Summary (DEN170018) Page 5 of 5
5. The NSS-2 BRIDGE includes the use of a transillumination technique to place the
device. SUMMARY OF NONCLINICAL/BENCH STUDIES New biocompatibility, electrical safety, electromagnetic compatibility, shelf life, sterility, and software testing was not required for the NSS-2 BRIDGE device as the device is nearly identical to the EAD device cleared in K140530. In the sections below, the testing provided for the K140530 submission is summarized to support the safety and effectiveness of this device for its intended use (see the 510(k) Summary for K140530 for more information). The technological changes detailed above do not impact any results of the testing. Additional information on these changes and why they do not impact the results of the testing are discussed in the associated sections below.
BIOCOMPATIBILITY/MATERIALS Biocompatibility information for DEN170018 was leveraged from data previously provided for the EAD device cleared under K140530.
Table 2: List of Patient-Contacting Materials Patient Contacting Device Component
Nature of Tissue Contact
Duration of Tissue Contact
Tweezers No skin contact No skin contact Transilluminator (pen light)
Behind ear < 1 minute Material biocompatibility data provided.
Kitted Bag containing Fixation Plasters
Over needle arrays on front surface of ear
Up to 120 hours Material biocompatibility data provided.
Surgical Marker On front surface of ear
Up to 120 hours Material biocompatibility data provided.
Up to 120 hours Materials used in the needle arrays are identical to the materials used in the 510(k)-cleared EAD (K140530).
Foam Adhesives Behind ear Up to 120 hours Foam adhesive material is identical to the materials used in the 510(k)-cleared EAD (K140530)
Several changes were made in the NSS-2 BRIDGE device in comparison to the previously cleared device in K140530:
De Novo Summary (DEN170018) Page 6 of 6
1. The EAD wire harness array has 4 leads: three 4-needle arrays and one single-needle lead. The NSS-2 BRIDGE additional wire harness has 4 leads: one 4-needle array, and three single-needle leads.
2. A pen light is included in the NSS-2 BRIDGE kit. 3. The material for the EAD housing is The material of the PNFS signal
generator housing is The tweezers, transilluminator (pen light), alcohol swab, and surgical marker are Class I, 510(k)-exempt products packaged as part of the convenience kit. The fixation plasters and foam adhesive were tested for cytotoxicity, sensitization, and irritation in K140530 per FDA Blue Book Memorandum #G95-1 “Use of International Standard ISO-10993, ‘Biological Evaluation of Medical Devices Part 1: Evaluation and Testing,’” May 1, 1995, and International Standard ISO 10993-1 “Biological Evaluation of Medical Devices − Part 1: Evaluation and Testing Within a Risk Management Process,” as recognized by FDA. All results demonstrated acceptable performance. The medical grade titanium of the percutaneous electrode arrays that comes into contact with the patient is identical to the medical grade titanium of the previously cleared percutaneous electrodes (K140530) in formulation, processing, sterilization, and geometry, and no other chemicals have been added (e.g., plasticizers, fillers, color additives, cleaning agents, mold release agents). Though the needle array configuration was changed for the NSS-2 BRIDGE device, this change does not impact the biocompatibility of the needles and no additional testing was requested. The material of the PNFS generator’s plastic housing changed from which may adversely impact the biocompatibility of the device. However, the plastic housing is not patient contacting because 510(k)-cleared foam adhesive is used to prevent transient contact of the housing with the patient. SHELF LIFE/STERILITY Shelf life and sterility information was largely leveraged from information previously provided for the EAD device cleared under K140530 because there have been no changes to the sterilization method, shelf life, or packaging with the NSS-2 BRIDGE, which has an additional wire harness option with 4 percutaneous leads: three single-needle leads, and one 4-needle array (a “1-1-1-4” harness configuration). Sterilization Validation was conducted on the wire harness percutaneous electrode arrays using the using the VDMAX25 method according to ISO 11137-2:2007 “Sterilization of health care products -- Radiation -- Part 2: Establishing the sterilization dose” and demonstrated that a sterility assurance level (SAL) of 10-6 was accomplished with
kGy. The device fulfilled the requirements of sterility according to ISO 11737-2:2009 “Sterilization of medical devices -- Microbiological methods -- Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization
(b) (4)
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De Novo Summary (DEN170018) Page 10 of 10
Presence of Poly-drug Use (%) Marijuana 15 (21) Benzodiazepines 13 (18) Cocaine 2 (.03) Alcohol 0 (0)
All patients who received the NSS-2 BRIDGE device were enrolled in the study. In this group of patients (n=73), the mean COWS score prior to NSS-2 BRIDGE placement was 20.1 (±6.1). Twenty minutes after NSS-2 BRIDGE placement, the mean score was reduced by 62.7% to 7.5 (±5.9) (p<0.001 vs baseline scores).
The mean score continued to decrease after 30 minutes to 4.0 (±4.4) and 60 minutes to 3.1 (±3.4) (84.6% reduction, p<0.001 vs baseline scores). No rescue medications were used during this period. On day 5, a total of 64 patients returned to the clinic for medically assisted therapy (MAT) demonstrating a successful MAT transition for 88.8% of the patients (64/73). Of these 64 patients, the COWS score was only recorded for thirty-three (33) patients. The mean withdrawal score for this subset of 33 patients on day 5 was 0.6 (97.1% reduction, p<0.001 vs baseline scores). All patients who transitioned to MAT had a negative urine toxicology screen for opioids prior to administering the MAT. Overall, 73/73 (100%) subjects had a reduction in COWS scores by 30 minutes with a minimum decrease of at least 31%. The results are shown in Figure 6.
Figure 6. Opioid withdrawal scores before and after NSS-2 BRIDGE device
placement. A significant decrease in the clinical opioid withdrawal scale (COWS) scores was seen after applications of the device at all time points measured
(*p<0.001 vs baseline scores). Results are based on a total number of 73 patients who received the NSS-2 BRIDGE device.
De Novo Summary (DEN170018) Page 11 of 11
At 60 minutes 57/73 (78.0%) had withdrawal scores of ≤ 3. During the entire 5 day period, no anti-psychotic, narcotic or benzodiazepine medications were given. Thirty eight percent (28/73) of patients received an antiemetic. Safety analysis No adverse events were recorded in any subject during the entire time of neurostimulation with the NSS-2 BRIDGE. Percutaneous therapies, generally, have risks of bleeding or infection at the puncture site, or skin irritation or pain at the site of application. A separate study was performed to quantify percutaneous nerve field stimulator (PNFS) safety. In the retrospective chart review of the placement of 1207 PNFS devices including the NSS-2 BRIDGE (19312 punctures) across 6 US sites for a variety of indications, there were the following adverse events: bleeding (n=11), pain (n=2), dermatitis (n=11). All events were resolved spontaneously following removal of the device (Roberts A, Sithole A, Sedghi M, Walker CA, Quinn TM. Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. Medical Devices (Auckland, NZ). 2016;9:389-393. doi:10.2147/MDER.S107426). This study only reported safety data and did not include effectiveness data. Pediatric Extrapolation In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population under 18 years of age. LABELING Labeling for the NSS-2 BRIDGE resembles labeling previously provided for the EAD device cleared under K140530. The NSS-2 BRIDGE Instructions for Use are consistent with the clinical data and cover all the hazards and other clinically relevant information that may impact use of the device. The labeling includes the following contraindications:
Use of cardiac pacemakers because no clinical data is available; Hemophilia; Psoriasis vulgaris;
and clarifies that an intact skin surface is essential for the use of NSS-2 BRIDGE stimulator. A summary of the clinical data used to support the proposed intended use is provided including a description of the risks and adverse events associated with normal use of the NSS-2 BRIDGE device. The labeling provides adequate instructions for use to inform the health care provider in the correct placement and safe use of the NSS-2 BRIDGE including information on the shelf life and technical parameters of the device. The labeling satisfies the requirements of 21 CFR § 801.109. RISKS TO HEALTH The table below identifies the risks to health that may be associated with use of a percutaneous nerve stimulator for substance use disorders and the measures necessary to mitigate these risks.
De Novo Summary (DEN170018) Page 13 of 13
BENEFIT/RISK DETERMINATION The risks of the device are based on nonclinical laboratory data as well as data collected in a clinical study described above.
No adverse events were noted in the study of opioid withdrawal (n=73).
In the retrospective chart review of 1207 patients receiving PNFS devices including the NSS-2 BRIDGE (this represents 19312 punctures) across 6 US sites for a variety of indications, the following adverse events were observed: bleeding (n=11), pain (n=2), dermatitis (n=11). All events resolved spontaneously following removal of the device (Roberts A, Sithole A, Sedghi M, Walker CA, Quinn TM.; ‘Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study’. Medical Devices (Auckland, NZ). 2016;9:389-393. doi:10.2147/MDER.S107426.). Percutaneous therapies, generally, have risks of bleeding or infection at the puncture site, or skin irritation or pain at the site of application. No infections have been noted in the use of this device. The probable benefits of the device are also based on data collected in a clinical study as described above.
This study demonstrated that individuals who received the NSS-2 BRIDGE device had a clinical benefit as shown by a change in the COWS of, on average, greater than 15%. A COWS score change of 15% for a given individual is considered clinically significant (Wesson and Ling 2003, Tompkins et al 2009). Twenty minutes after NSS-2 placement, there was a mean 62.7% reduction in the COWS. At 60 minutes into the treatment of withdrawal with this device, there was a mean 84.6% reduction in the COWS. The risks are minimal, limited, and rarely occur. Even though individual level analyses are not available, the results indicate that the benefits compared to the risks are favorable.
Additional factors to be considered in determining probable risks and benefits for the NSS-2 BRIDGE include:
The study used to support this indication was a single-arm, open label, multi-center retrospective study. The lack of controls increases the uncertainty of the placebo effect.
Variations exist amongst the eight outpatient clinics with an approximate daily patient
volume ranging from 4 to 25. Because the clinics varied in terms of patient volume, the standard of care in addition to the use of this device may also have varied in undetermined ways.
It is not clear if any other inclusion or exclusion criteria, for example, medical history or concomitant medicine were also used to select subjects who were treated in these eight clinics. It is also not clear how many patients were screened initially from the eight clinics and, among those who were screened, how many failed to meet enrollment criteria.
De Novo Summary (DEN170018) Page 14 of 14
The study did not include a long-term evaluation of safety and effectiveness or information on repeated use.
Day 5 COWS scores were not recorded for 40/73 subjects, however 64/73 (88.8%) successfully transitioned to medically assisted therapy (MAT). All patients who transitioned to MAT had a negative urine toxicology screen for opioids prior to administering the MAT. The effects of opioid withdrawal typically dissipate by Day 5 with or without the use of the subject device.
While factoring these considerations into our decision, the clinical results, especially at one hour, suggest a probable benefit of the device. References Tompkins DA, Bigelow GE, Harrison JA, Johnson RE, Fudala PJ, Strain EC. Concurrent Validation of the Clinical Opiate Withdrawal Scale (COWS) and Single-Item Indices against the Clinical Institute Narcotic Assessment (CINA) Opioid Withdrawal Instrument. Drug and alcohol dependence. 2009;105(1-2):154-159. Wesson DR, Ling W. The Clinical Opioid Withdrawal Scale. J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9. Patient Perspectives This submission did not include specific information on patient perspectives for this device. Benefit/Risk Conclusion In conclusion, given the available information above, the data support use as an aid to reduce the symptoms of opioid withdrawal, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination. The probable benefits outweigh the probable risks for the NSS-2 BRIDGE. The device provides substantial benefits and the risks can be mitigated by the use of general and the identified special controls. CONCLUSION The De Novo request for the NSS-2 BRIDGE is granted and the device is classified under the following:
Product Code: PZR Device Type: Percutaneous nerve stimulator for substance use disorders Class: II Regulation: 21 CFR 882.5896
